Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([OH:6])[CH2:2][CH2:3][C:4]#[CH:5].I[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14]>C(NCC)C>[CH3:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:5]#[C:4][CH2:3][CH2:2][CH2:1][OH:6]
Reactant: C#CCCCO
Reactant: Cc1ccccc1I
Solvent: CCNCC
Product: Cc1ccccc1C#CCCCO
Temperature: 25 °C
Reaction time: 24 h
Yield: 59.4 %

Procedure:
A mixture of 4-pentyn-1-ol (1 g, 12.1 mmol), 2-iodotoluene (2.53 g, 11.6 mmol), dry diethylamine (20 ml), bis-triphenyl-phosphine palladium (II) chloride (150 mg) and cuprous iodide (60 mg) was stirred at room temperature under dry nitrogen for 24 hours. The solvent was removed and the residue extracted with ether. The organic phase was washed with brine and dried and the solvent removed. The crude product was purified by dry column chromatography (alumina, 9:1 hexane:ether 1:1 hexane:ether) to give 1.2 g (60% of theory) of 5-(2'-methylphenyl)-4-pentyn-1-ol as a brown oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH:16]#[C:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(CC)CC)C.N1C=CC=CC=1>[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[C:18]1([C:17]#[C:16][C:2]2[CH:3]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([CH:11]=2)[C:7]([O:9][CH3:10])=[O:8])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: COC(=O)c1cc(Br)cc(C(=O)OC)c1
Reactant: C#Cc1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccncc1
Solvent: O
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(C#Cc2ccccc2)cc(C(=O)OC)c1
Yield: 75 %

Procedure:
In a 1 L four-neck flask equipped with a thermometer, a Dimroth condenser, a nitrogen introduction tube and an agitator, 99.7 g (0.365 mol) of the second intermediate (dimethyl 5-bromoisophthalate), 1.1 g (0.00419 mol) of triphenylphosphine, 0.275 g (0.00144 mol) of copper iodide and 41.0 g (0.401 mol) of phenylacethylene were charged and nitrogen was passed into the flask. Then, 375 mL of dehydrated triethylamine and 200 mL of dehydrated pyridine were added therein and the mixture was agitated and dissolved. After passing the nitrogen for one hour, 0.3 g (0.000427 mol) of dichlorobis(triphenyl phosphine)palladium was quickly added and the mixture was heated and refluxed in an oil bath for one hour. Then, triethylamine and pyridine were removed under reduced pressure to obtain a brown viscous solution. The solution was added to 500 mL of water and filtered to separate a solid. The solid was washed with 500 mL of water, 500 mL of 5 mol/L hydrochloric acid and 500 mL of water each two times and dried under reduced pressure at 50° C. Thus, 80.6 g of dimethyl 5-phenylethynylisophthalate was obtained (the yield was 75%).
Reaction SMILES: [CH2:1](O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[CH2:12].[CH3:14][S:15](Cl)(=[O:17])=[O:16].C(N(CC)CC)C.O>ClCCl>[CH3:14][S:15]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[CH2:12])(=[O:17])=[O:16]
Reactant: CS(=O)(=O)Cl
Reactant: C=CCCCCCCCCCCO
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=CCCCCCCCCCCS(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of 11-dodecen-1-ol (5.5 g, 29.9 mmol) in dichloromethane (70 mL) at 0° C. was added methanesulfonyl chloride (3.55 g, 2.40 mL, 31.0 mmol) followed by triethylamine (4.38 g, 46.0 mmol). After stirring for 10 minutes at 0° C., the reaction was allowed to warm to 25° C. and stirred for 2 hours. The reaction was poured into water (60 mL), separated and washed with dichloromethane (50 mL). The organic portions were combined, dried using magnesium sulfate, and evaporated to yield 12-methanesulfonyl-1-dodecene as a yellow oil which was then used without further purification.
Reaction SMILES: [CH:1]1([N:7]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[C:8](=[O:23])[NH:9][C:10]2[S:11][C:12]([S:15]([NH:18][CH2:19][C:20]([OH:22])=[O:21])(=[O:17])=[O:16])=[CH:13][N:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:30]1(N[C@H]2CC[C@H](C)CC2)CCCC[CH2:31]1.[CH2:44](OC(C1(NS(C2SC(N)=NC=2)(=O)=O)CC1)=O)C>>[CH:24]1([N:7]([C@H:1]2[CH2:2][CH2:3][C@H:4]([CH3:44])[CH2:5][CH2:6]2)[C:8](=[O:23])[NH:9][C:10]2[S:11][C:12]([S:15]([NH:18][C:19]3([C:20]([OH:22])=[O:21])[CH2:31][CH2:30]3)(=[O:16])=[O:17])=[CH:13][N:14]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: O=C(O)CNS(=O)(=O)c1cnc(NC(=O)N(C2CCCCC2)C2CCCCC2)s1
Reactant: C[C@H]1CC[C@H](NC2CCCCC2)CC1
Reactant: CCOC(=O)C1(NS(=O)(=O)c2cnc(N)s2)CC1
Product: C[C@H]1CC[C@H](N(C(=O)Nc2ncc(S(=O)(=O)NC3(C(=O)O)CC3)s2)C2CCCCC2)CC1

Procedure:
Prepared in a similar manner to [2-(3,3-dicyclohexyl-ureido)-thiazole-5-sulfonylamino]-acetic acid via cyclohexyl-(trans-4-methyl-cyclohexyl)-amine and 1-(2-amino-thiazole-5-sulfonylamino)-cyclopropanecarboxylic acid ethyl ester to give the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:15])[NH:7][CH:8]([CH3:14])[C:9](=[O:13])[CH:10]=[N+]=[N-])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC>C(Cl)Cl.C([O-])(=O)C.[Rh+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:7]1[CH2:10][C:9](=[O:13])[CH:8]1[CH3:14])=[O:15])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(NC(=O)OC(C)(C)C)C(=O)C=[N+]=[N-]
Agent: [Rh+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1C(=O)CN1C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 1 h

Procedure:
(3-Diazo-1-methyl-2-oxo-propyl)-carbamic acid tert-butyl ester (0.250 g, 1.17 mmol) was dissolved in anhydrous DCM (6 mL) and Et3N (1.18 mg, 0.012 mmol) was added. The reaction mixture was cooled to 0° C. and rhodium (II) acetate (0.010 g, 0.023 mmol) was added. The reaction mixture was stirred at 0° C. for 1 h then concentrated in vacuo to give 2-methyl-3-oxo-azetidine-1-carboxylic acid tert-butyl ester, which was used in the next step without further purification. TLC (eluting with 20% EtOAc/heptane) Rf=0.3.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[N:8][C:9]([OH:10])=[C:4]2[CH:3]=[N:2]1.[Br:11]Br>O>[Br:11][C:3]1[C:4]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[OH:10])[NH:1][N:2]=1
Reactant: Oc1ncnc2[nH]ncc12
Reactant: BrBr
Solvent: O
Product: Oc1ncnc2[nH]nc(Br)c12
Temperature: 91 °C
Yield: 9.5 %

Procedure:
1H-pyrazolo[3,4-d]pyrimidin-4-ol (10 g, 73.5 mmol) was suspended in 700 ml of water. Bromine (10 ml, 194 mmol) was added and the resulting reaction mixture was heated to 91° C. overnight. After cooling on ice-water, the solid was collected by filtration to give 1.508 g of 3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-ol as light yellow solid. 1H NMR (DMSO) 8.06 (s, 1H), 12.25(bs, 1H), 14.06 (bs, 1H).
Reaction SMILES: [CH2:1]([N:4]([CH2:8][C:9]#[CH:10])[CH2:5][C:6]#[CH:7])[C:2]#[CH:3].[CH2:11]([O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][Br:29])=[CH:26][CH:25]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>CC(C)=O>[Br-:29].[CH2:11]([O:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][N+:4]([CH2:8][C:9]#[CH:10])([CH2:5][C:6]#[CH:7])[CH2:1][C:2]#[CH:3])=[CH:26][CH:25]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: C#CCN(CC#C)CC#C
Reactant: CCCCCCCCCCCCOc1ccc(CBr)cc1
Solvent: CC(C)=O
Product: C#CC[N+](CC#C)(CC#C)Cc1ccc(OCCCCCCCCCCCC)cc1
Product: [Br-]
Reaction time: 72 h
Yield: 50.8 %

Procedure:
Tripropargylamine (0.85 mL, 9 mmol) in acetone (6 mL) was slowly added to a solution of 4-(dodecyloxy)benzyl bromide (3.01 g, 8.5 mmol) in acetone (10 mL). After 3 d at room temperature, acetone was removed in vacuo and the residue purified by column chromatography over silica gel with CH2Cl2/MeOH=20/1 to 10/1 as the eluents to give a white powder (2.1 g, 61%). 1H NMR (400 MHz, CDCl3, δ): 7.56 (d, J=8.4 Hz, 2H), 7.08 (d, J=8.4 Hz, 2H), 4.62 (s, 2H), 4.32 (s, 6H), 4.22 (s, 3H), 4.02 (t, J=6.4 Hz, 2H), 1.73-1.68 (m, 2H), 1.40-1.24 (m, 18H), 0.87 (t, J=5.6 Hz, 3H); 13C NMR (100 MHz, CDCl3, δ) 161.6, 134.2, 130.4, 117.2, 115.5, 114.7, 76.6, 75.3, 68.3, 68.0, 63.5, 49.7, 41.9, 29.6, 29.4, 29.3, 29.1, 26, 22.7, 14.1; ESI-MS (m/z): [M−Br]+ calcd for C28H40NO+ 406, found 406.
Reaction SMILES: Cl[C:2](Cl)=[N:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.[NH2:17][CH2:18][CH2:19][CH2:20][NH2:21].C(N(CC)CC)C>C(#N)C>[CH2:10]([C:7]1[CH:6]=[CH:5][C:4]([N:3]=[C:2]2[NH:21][CH2:20][CH2:19][CH2:18][NH:17]2)=[CH:9][CH:8]=1)[CH2:15][CH2:14][CH2:13][CH2:12][CH3:11]
Reactant: NCCCN
Reactant: ClC(Cl)=Nc1ccc(C2CCCCC2)cc1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCCCCCc1ccc(N=C2NCCCN2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 2.6 g of N-dichloromethylene 4-cyclohexylaniline in 40 ml of acetonitrile is added dropwise to a solution of 1 ml of 1,3-diaminopropane in 20 ml of acetonitrile in 15 minutes at room temperature. After the addition of 1 ml of triethylamine, the solution is stirred for 1 hour at room temperature, after which the reaction mixture is filtered while warm. After distilling off the solvent the residue is taken up in ether and successively washed with 2 N sodium hydroxide solution and water. The ether layer is dried and evaporated, after which the residue is recrystallized from acetonitrile. The resulting 2-(4-cyclohexylphenyl)imino-hexahydropyrimidine has a melting point of 180°-182° C. 2-(4-n-hexylphenyl)imino-hexahydropyrimidine was prepared in a corresponding manner.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[C:5]([Br:7])[N:6]=1.[O:8]=[S:9]1(=[O:36])[CH2:14][CH2:13][CH:12]([C:15]2[C:23]3[C:18](=[C:19]([C:33]([NH2:35])=[O:34])[CH:20]=[C:21](B4OC(C)(C)C(C)(C)O4)[CH:22]=3)[NH:17][CH:16]=2)[CH2:11][CH2:10]1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Br:7][C:5]1[N:6]=[C:2]([C:21]2[CH:22]=[C:23]3[C:18](=[C:19]([C:33]([NH2:35])=[O:34])[CH:20]=2)[NH:17][CH:16]=[C:15]3[CH:12]2[CH2:11][CH2:10][S:9](=[O:8])(=[O:36])[CH2:14][CH2:13]2)[S:3][CH:4]=1
Reactant: Brc1csc(Br)n1
Reactant: CC1(C)OB(c2cc(C(N)=O)c3[nH]cc(C4CCS(=O)(=O)CC4)c3c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: NC(=O)c1cc(-c2nc(Br)cs2)cc2c(C3CCS(=O)(=O)CC3)c[nH]c12
Reaction time: 0.67 h
Yield: 4.6 %

Procedure:
To a microwave vial was added 2,4-dibromo-1,3-thiazole (0.035 g, 0.143 mmol), 3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide (0.060 g, 0.143 mmol) and potassium carbonate (0.059 g, 0.429 mmol) along with 1,4-dioxane (1.073 mL)/water (0.358 mL). The mixture was degassed with nitrogen and Pd(PPh3)4 (0.017 g, 0.014 mmol) was added. The reaction mixture was heated in the microwave under ‘high’ absorption setting for 40 minutes at 150° C. The reaction mixture was filtered through a Thiol SPE cartridge (500 mg) eluting with 1:1 MeOH/DCM (10 mL). The eluent was concentrated under nitrogen and purified by RP-HPLC on an X-Bridge C18 column with Acetonitrile/Water (0.1% NH4OH), giving 3 mg (4.6%) of the title compound.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:23]([C:24]([F:27])([F:26])[F:25])=[N:22][N:21]=[N:20]2)=[CH:15][C:14]=1[C:28]1[CH2:29][O:30][C:31]2([CH2:37][CH2:36][CH2:35][NH:34][CH2:33]2)[CH:32]=1>N1C=CC=CC=1>[C:1]([N:34]1[CH2:35][CH2:36][CH2:37][C:31]2([O:30][CH2:29][C:28]([C:14]3[CH:15]=[C:16]([N:19]4[C:23]([C:24]([F:25])([F:26])[F:27])=[N:22][N:21]=[N:20]4)[CH:17]=[CH:18][C:13]=3[O:12][CH3:11])=[CH:32]2)[CH2:33]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: COc1ccc(-n2nnnc2C(F)(F)F)cc1C1=CC2(CCCNC2)OC1
Agent: Cl
Solvent: c1ccncc1
Product: COc1ccc(-n2nnnc2C(F)(F)F)cc1C1=CC2(CCCN(C(=O)c3ccccc3)C2)OC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 67.8 %

Procedure:
Benzoyl chloride (0.10 ml, 0.86 mmol) was added to a solution of 3-(2-methoxy-5-(5-trifluoromethyl-1H-tetrazol-1-yl)phenyl)-1-oxa-7-azaspiro[4,5]dec-3-ene hydrochloride (Desc. 11; 0.33 g, 0.79 mmol) in pyridine (5 ml) at 0° C. The mixture was stirred at 0° C. for 11/2 hours, allowed to warm to room temperature and concentrated in vacuo. 1M Hydrochloric acid (50 ml) was added to the residue and the mixture extracted with dichloromethane (2×25 ml). The combined extracts were dried (MgSO4), concentrated and the residue purified by flash chromatography, eluting with 21/2% methanol in dichloromethane, to afford the title compound as a white foam (0.26 g, 68%), which was recrystallised from ethyl acetate/hexane, m.p. 154°-156° C.; (Found: C, 59.29; H, 4.45; N, 14.15, C24H33F3N5O3 requires C, 59.38; H, 4.57; N, 14.43%); δH (360MHz, DMSO-d6, 353K) 1.62 (1H, m), 1.75-1.85 (3H, m), 3.19 (1H, m), 3.39 (1H, br d, J 12Hz), 3.49 (1H, m), 3.80 (1H, m), 3.94 (3H, s, ArOCH3), 4.74 (1H, m, 2-CHaHB), 4.89 (1H, dd, J 12.6, 1.9Hz, 2--CHAHB), 6.52 (1H, br s, 4--CH=), 7.30 (1H, d, J 8.8Hz, 3'-H), 7.37 (5H, m, PhH), 7.55 (1H, d, J 2.6Hz, 6'-H), 7.63 (1H, dd, J 8.8, 2.6Hz, 4'-H); m/z (ES+) 486 ([M+H]+).
Reaction SMILES: CO.[CH:3]1[CH2:7][CH:6]=[CH:5][CH:4]=1.[CH:8](=O)[C:9]1[O:13][CH:12]=[CH:11][CH:10]=1.[CH2:15](NCC)C>O>[CH2:8]([C:4]1[C:3](=[CH2:15])[CH:7]=[CH:6][CH:5]=1)[C:9]1[O:13][CH:12]=[CH:11][CH:10]=1
Reactant: C1=CCC=C1
Reactant: O=Cc1ccco1
Reactant: CCNCC
Solvent: CO
Solvent: O
Product: C=C1C=CC=C1Cc1ccco1
Reaction time: 2 h

Procedure:
Into a glass reactor equipped with a nitrogen inlet is charged methanol (238 ml), freshly distilled cyclopentadiene (2 moles), furfural (2 moles) and diethylamine (8 ml). The resulting reaction is slightly exothermic. The dark red solution is stirred for 71/2 hours. At this time an equal volume of distilled water is added and extracted with chloroform. The organic layer is dried and evaporated leaving a dark red viscous oil as the product, furfuryl fulvene.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)=[CH:16][CH:17]=2)=[CH:11][C:10]([C:28](O)=[O:29])=[N:9]1.CN(C=O)C.C(Cl)(=O)C([Cl:39])=O.O1CCOCC1>C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:25])=[O:26])[CH:19]=3)=[CH:16][CH:17]=2)=[CH:11][C:10]([C:28]([Cl:39])=[O:29])=[N:9]1
Reactant: O=C(Cl)C(=O)Cl
Reactant: CS(=O)(=O)c1cccc(-c2ccc(-c3cc(C(=O)O)nn3-c3ccccc3Cl)s2)c1
Solvent: CN(C)C=O
Solvent: c1ccccc1
Solvent: C1COCCO1
Product: CS(=O)(=O)c1cccc(-c2ccc(-c3cc(C(=O)Cl)nn3-c3ccccc3Cl)s2)c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a suspension of 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)thiophen-2-yl)-1H-pyrazole-3-carboxylic acid (160 mg, 0.35 mmol) in PhH (1.0 mL) was added a small amount of DMF. Oxalyl chloride (60 μL, 0.69 mmol) was added to the suspension. After stirring for 15 minutes at ambient temperature, gas evolution had ceased and only part of the solids had dissolved. After 25 minutes dioxane (2.0 mL) was added. There was renewed gas evolution and most of the solids dissolved. After 30 minutes additional oxalyl chloride (50 μL, 0.57 mmol) was added. There was vigorous gas evolution and after a total of 90 minutes stirring the reaction mixture was concentrated under reduced pressure to afford 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)thiophen-2-yl)-1H-pyrazole-3-carbonyl chloride as a pale brown foam. This material was carried on to the subsequent acylation without purification.
Reaction SMILES: [Cl:1][C:2]([Cl:20])([Cl:19])[CH2:3][O:4][C:5]([CH2:7][O:8][N:9]=[C:10]([C:16](=[O:18])[CH3:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:6].S(Cl)([Cl:24])(=O)=O.O.C(Cl)Cl>C(O)(=O)C>[Cl:1][C:2]([Cl:19])([Cl:20])[CH2:3][O:4][C:5]([CH2:7][O:8][N:9]=[C:10]([C:16](=[O:18])[CH2:17][Cl:24])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:6]
Reactant: CCOC(=O)C(=NOCC(=O)OCC(Cl)(Cl)Cl)C(C)=O
Reactant: O=S(=O)(Cl)Cl
Solvent: O
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCOC(=O)C(=NOCC(=O)OCC(Cl)(Cl)Cl)C(=O)CCl
Temperature: 40 °C
Reaction time: 7 h
Yield: 100.7 %

Procedure:
A mixture of ethyl 2-(2,2,2-trichloroethoxycarbonylmethoxyimino)-3-oxobutyrate (20 g) and sulfuryl chloride (7.7 g) in acetic acid (20 ml) was stirred at 40° C. for 7 hours. After the reaction mixture was added to a mixture of water (100 ml) and methylene chloride (100 ml) with stirring, the separated organic layer was washed with 5% aqueous sodium bicarbonate and water, followed by drying over magnesium sulfate. Removal of the solvent gave ethyl 2-(2,2,2-trichloroethoxycarbonylmethoxyimino)-4-chloro-3-oxobutyrate (22 g).
Reaction SMILES: [CH2:1]([C:6]1[CH2:7][CH:8]([CH2:17]O)[S:9][CH2:10][C:11]=1[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:2][CH2:3][CH2:4][CH3:5].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:39]>C(Cl)Cl>[Br:39][CH2:17][CH:8]1[CH2:7][C:6]([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])=[C:11]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:10][S:9]1
Reactant: CCCCCC1=C(CCCCC)CC(CO)SC1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCCCCC1=C(CCCCC)CC(CBr)SC1
Temperature: 0 °C
Reaction time: 14 h

Procedure:
Part B. The alcohol from Part A above is dissolved in methylene chloride along with carbon tetrabromide, and cooled to 0° C. A methylene chloride solution of triphenylphosphine is added dropwise. The mixture is stirred for 14 hours, then evaporated and rapidly eluted through a plug ofsilica gel with an appropriate solvent system to afford 2-bromomethyl-3,6-dihydro-4,5-dipentyl-2H-thiopyran. This compound is useddirectly, and treated with potassium cyanide in dimethylsulfoxide at 80° C. until thin-layer chromatography shows the reaction is complete. At this point, the solution is cooled, and poured into 4 volumesof water. This mixture is extracted with ethyl acetate, and the extract is washed with more water (3× an equal volume), then brine, then dried over anhydrous magnesium sulfate, filtered and evaporated. Chromatography will then purify the product, (3,6-dihydro-4,5-dipentyl-2H-thiopyran-2-yl)acetonitrile.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:13](=[C:14]3[C:19]=1[CH:18]=[CH:17][CH:16]=[CH:15]3)[CH:12]=[CH:11][C:10]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]2=1.[Br:20]N1C(=O)CCC1=O>ClC1C=CC=CC=1.CO.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:20][CH2:1][C:2]1[CH:3]=[C:4]2[C:13](=[C:14]3[C:19]=1[CH:18]=[CH:17][CH:16]=[CH:15]3)[CH:12]=[CH:11][C:10]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]2=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cc2c3ccccc3ccc2c2ccccc12
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: CO
Solvent: Clc1ccccc1
Product: BrCc1cc2c3ccccc3ccc2c2ccccc12
Temperature: 50 °C
Reaction time: 1 h
Yield: 75.8 %

Procedure:
A solution of 6-methylchrysene (4,85 g, 20 mmol), N-bromosuccinimide (3.60 g, 20.2 mmol), and benzoyl peroxide (0.242 g, 1.0 mmol) in chlorobenzene (100 mL) was heated under nitrogen at 80° C. After 1 hour, NMR analysis indicated that the starting material had been consumed. The solution was cooled to 50° C. at which point a solid precipitate had formed. The mixture was diluted with methanol (100 mL) and further cooled to ambient temperature. The mixture was filtered and the solid washed with methanol to give 4.87 g (76% yield) of 6-bromomethylchrysene. 1H NMR (CDCl3) 5.17 (s, 2H), 7.25 (m, 4 H), 8.0 (t, J=8.7 Hz, 2 H), 8.31 (m, 1 H), 8.67 (d, J=9.0 Hz), 8.75 (d, J=9.0 Hz, 1 H), 8.81 (m, 2 H).
Reaction SMILES: [OH:1][C@H:2]1[CH2:17][C:16](=[O:18])[O:15][O:14][C@H:13](/[CH:19]=[CH:20]/[CH2:21][CH2:22][S:23]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:12][C:11](=[O:43])[NH:10][C@H:9]([CH:44]([CH3:46])[CH3:45])[C:8](=[O:47])[NH:7][C@H:6]([CH3:48])[C:5](=[O:49])[NH:4][C@@H:3]1[CH:50]([CH3:52])[CH3:51].C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:1][C@H:2]1[CH2:17][C:16](=[O:18])[O:15][O:14][C@H:13](/[CH:19]=[CH:20]/[CH2:21][CH2:22][SH:23])[CH2:12][C:11](=[O:43])[NH:10][C@H:9]([CH:44]([CH3:46])[CH3:45])[C:8](=[O:47])[NH:7][C@H:6]([CH3:48])[C:5](=[O:49])[NH:4][C@@H:3]1[CH:50]([CH3:52])[CH3:51]
Reactant: CC(C)[C@H]1NC(=O)[C@@H](C)NC(=O)[C@@H](C(C)C)NC(=O)C[C@@H](/C=C/CCSC(c2ccccc2)(c2ccccc2)c2ccccc2)OOC(=O)C[C@@H]1O
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)[C@H]1NC(=O)[C@@H](C)NC(=O)[C@@H](C(C)C)NC(=O)C[C@@H](/C=C/CCS)OOC(=O)C[C@@H]1O
Reaction time: 1.5 h
Yield: 9.1 %

Procedure:
To a solution of 9 (8 mg, 0.011 mmol) in CH2Cl2 (1 mL) was added triethylsilane (7 μL, 0.44 mmol) was added dropwise TFA (0.2 mL, 20% v/v). After stirring for 1.5 h the reaction was concentrated in vacuo and purified by flash column chromatography (eluent 1:0-99:1-98:2-97:3-96.4 CH2Cl2/MeOH) to give the product 10 (0.47 mg, 0.001 mmol, 9%) as a white solid: Rf 0.44 MeOH/CH2Cl2 (1:9); MS (ES+) 584.2 (100%, [M+Na]+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH2:9][CH2:10][N:11]([CH3:19])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH2:18])=[CH:4][CH:3]=1.[C:26](N1C=CN=C1)(N1C=CN=C1)=[O:27].[NH:38]([C:42]1[S:43][CH:44]=[C:45]([CH2:47][S:48][CH2:49][CH2:50][NH2:51])[N:46]=1)[C:39]([NH2:41])=[NH:40]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH2:9][CH2:10][N:11]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:26]([NH:51][CH2:50][CH2:49][S:48][CH2:47][C:45]2[N:46]=[C:42]([NH:38][C:39]([NH2:41])=[NH:40])[S:43][CH:44]=2)=[O:27])[CH3:19])=[CH:4][CH:3]=1
Reactant: N=C(N)Nc1nc(CSCCN)cs1
Reactant: CN(CCCCCCN)CCC(c1ccc(Cl)cc1)c1ccccn1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: CN(CCCCCCNC(=O)NCCSCc1csc(NC(=N)N)n1)CCC(c1ccc(Cl)cc1)c1ccccn1

Procedure:
Preparation is effected analogously to Example 63, using 0.9 g (2.5 mmol) of N-[3-(4-chlorophenyl)-3-(2-pyridyl)propyl]-N-methyl-1,6-hexanediamine, an equimolar amount of 1,1'-carbonyldiimidazole and 0.6 g (2.6 mmol) of 2-[[(2-guanidino-4-thiazolyl)methyl]thio]ethaneamine as starting materials. Working up by chromatography (eluant: methylene chloride) analogously to Example 63 yields the purified title compound in the form of an oil; MS (+FAB method): m/z (rel. int.[%])=617 ([M+H]+, 6), 230 (100), 155 (28); IR (KBr): 1641 cm-1 (C=O).
Reaction SMILES: F[C:2](F)(F)[C:3](O)=O.[N+](C1C=CC(COC(N=C(NC(OCC2C=CC([N+]([O-])=O)=CC=2)=O)N([CH2:23][C:24]([NH:26][CH:27]2[CH2:30]N[CH2:28]2)=O)C)=O)=CC=1)([O-])=O.[C:47](#N)C>O1CCCC1>[CH:27]([N:26]([CH2:2][CH3:3])[CH:24]([CH3:23])[CH3:47])([CH3:30])[CH3:28]
Reactant: O=C(O)C(F)(F)F
Reactant: CC#N
Reactant: CN(CC(=O)NC1CNC1)C(=NC(=O)OCc1ccc([N+](=O)[O-])cc1)NC(=O)OCc1ccc([N+](=O)[O-])cc1
Solvent: C1CCOC1
Product: CCN(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of (2S,4S) (4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline (888 mg) in anhydrous acetonitrile (15 ml), N,N'-carbonyldiimidazole (337 mg) was added, followed by stirring at room temperature for one hour. To the reaction mixture, N,N-diisopropylethylamine (330 μl) and a solution of the compound (1.69 g), which had been obtained in (2), in anhydrous tetrahydrofuran (16 ml) were added. The resulting mixture was treated in a similar manner to that described in Referential Example 16-(3), whereby the title compound (1.59 g) was obtained as an amorphous substance.